Abstract 1192P
Background
Tumour cells can induce immunotolerance, which can be reversed by checkpoint blockade immunotherapy, but response prediction remains a challenge. CD4+ T cells play an important role in activating adaptive immune responses. The functional state of CD4+ T cells is controlled by various signal transduction pathways. Over the past decade we have developed tests that quantitatively measure functional activities of signal transduction pathways (e.g. Hedgehog, Wnt, TGFβ Notch, NFκB, PI3K, JAK-STAT 1/2 and 3, and MAPK). We investigated the functional activity state of blood-derived CD4+ T cells from primary breast cancer patients.
Methods
CD4+ T cells were isolated from primary tumors, axillary lymph nodes and peripheral blood of 10 patients with untreated invasive primary breast carcinomas (4 ER/PR positive luminal patients, 1 ER/PR/HER2 positive patient, 5 triple negative patients) and blood of 4 healthy donors, and Affymetrix expression microarray data were generated (GSE36765). Signaling pathway activities were measured.
Results
In peripheral blood-derived CD4+ cells the JAK-STAT3 pathway was significantly more active compared to healthy individuals only (p=0.04); TGFβ pathway activity was highly variable, but on average not significantly, increased. In CD4+ T cells from tumor infiltrate (TIL), activity of FOXO, NFkB, JAK-STAT1/2, JAK-STAT3, and TGFβ signaling pathways was significantly increased compared to blood- and lymph node-derived CD4+ cells, reflecting the influence of the tumour environment.
Conclusions
In patient samples a varying mixture of resting, immune activated, and tolerant CD4+ T cells was probably present in blood and TIL, as had already been suggested based on previous bioinformatics analysis (J. Clin. Invest. 123, 2873–2892 (2013). Despite the heterogeneity, results indicate that in a subset of untreated primary cancer patients an immunotolerant pathway profile was present in blood-derived, and even stronger in TIL-derived, CD4+ T cells.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
Y. Wesseling-Rozendaal: Full/Part-time employment: Philips. A. Van De Stolpe: Full/Part-time employment: Philips. All other authors have declared no conflicts of interest.